The association between hypercholesterolemia and sitosterolemia, and report of a sitosterolemia kindred.

Abstract

BACKGROUND:

Sitosterolemia is associated with increases in intestinal sterol absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk.

OBJECTIVE:

We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case.

METHODS:

Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay.

RESULTS:

Of 207,926 subjects tested, 4.3% had LDL-C ≥190 mg/dL. Plasma β-sitosterol concentrations ≥8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (-29%) and β-sitosterol to 44.6 mg/L (-27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (-38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (-80% further decrease); and his β-sitosterol decreased to 14.1 mg/L (-68% further decrease).

CONCLUSIONS:

Our data indicate that about 4% of subjects with LDL-C concentrations ≥190 mg/dL have plasma β-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients.

• Authors: Eliot A Brinton, Paul N Hopkins, Robert A Hegele, Andrew S Geller, Eliana Y Polisecki, Margaret R Diffenderfer, Ernst J Schaefer
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2018 Jan - Feb Vol. 12 Issue 1 Pg. 152-161 ISSN: 1933-2874 [Print] United States
• PMID: 29169939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• ABCG8 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 8
• Anticholesteremic Agents
• Cholesterol, LDL
• Phytosterols
• Sitosterols
• gamma-sitosterol
• Ezetimibe

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 8 (genetics)
• Adolescent
• Adult
• Aged
• Anticholesteremic Agents (therapeutic use)
• Cholesterol, LDL (blood)
• Diet, Fat-Restricted
• Ezetimibe (therapeutic use)
• Female
• Heterozygote
• Humans
• Hypercholesterolemia (blood, complications, diagnosis, drug therapy)
• Intestinal Diseases (blood, complications, diagnosis)
• Lipid Metabolism, Inborn Errors (blood, complications, diagnosis)
• Male
• Middle Aged
• Phytosterols (adverse effects, blood)
• Sitosterols (blood)